Sutures are used to bring together ends of biological tissue and hold them in place until the joining tissues have time to heal. In patients with arterial occlusive disease, vascular surgeons use sutures to anastomose autogenous vein, prostehtic grafts, or arteries to other arteries in order to bypass around or replace diseased arterial segments. At virtually all inastomotic sites between the arteries and autogenous vein, or prosthetic grafts, a condition of rapid cellular growth termed "intimal hyperplasia" may occur.
Intimal hyperplasia (hereinafter "IH") is the usual response to blood vessel injury. This rapid cellular growth, as a response to injury of the blood vessel cellular lining (intima), begins to narrow (stenose) the opening (lumen) between the vessels and/or graft to the point where an occlusion may occur. More specifically, IH forms as a result of smooth muscle cell proliferation, migration, and extracellular matrix deposition. The interaction of platelets, macrophages, growth factors, and cytokines plays an important role in the process. There are systemic regimens to prevent the intimal hyperplatic response in animal models but none has proven beneficial in humans. IH is the primary cause of "restenosis" (narrowing) in the first year after vascular bypass operations and may cause indwelling venous catheters to occlude as well. Usually, the patient must have another operation to revise or replace the occluded graft. If a major vein occludes (i.e. jugular or subclavian) massive edema of the upper extremity, face and neck may occur and if an artery occludes, it could possibly lead to potential limb loss.
The most frequently performed prosthetic graft operation is an arterial to venous conduit for dialysis in chronic renal failure patients. Renal dialysis patients require repetitive angioaccess to this arterial-venous graft for dialysis to rid their system of toxins. The most commonly used graft for dialysis is a synthetic graft made from teflon or ePTFE (expanded polytetrafluroethylene). Unfortunately, these grafts rapidly fail and have a primary occlusion rate of 15% to 50% during the first year, with a mean patency of only 15 months. This failure in most cases is due to the development of intimal hyperplasia at the venous anastomosis.
In recent years studies have been conducted in animal models whose vessels have undergone angioplasty. It was found that the vessels response to injury from balloon angioplasty is similar to that observed at suture anastomotic lesions. Studies conducted at Emory University and Vanderbilt University suggest that "restenosis" (narrowing) results primarily from the migration and rapid proliferation of a smooth muscle type cell after balloon angioplasty. It has been demonstrated by these groups that very low levels of beta-particle irradiation introduced to the site of injury following angioplasty markedly inhibits smooth muscle cell proliferation and or migration. In a series of tissue culture experiments a 0.20 mm diameter titaniumwire was impregnated with low concentrations of 32P and these wires were placed in both rat and human smooth muscle cell cultures. The activity level of the wire ranged from 0.002 to 0.06 uCi/cm wire. In comparison to the control with no radiation it was found that in cultures where the wire activity was &gt;0.0006 uCi/cm there was a distinct zone of complete smooth muscle cell inhibition ranging from 5.5 to 10.6 mm from the radioactive wire. It was hypothesized that if a low level radioactive wire could induce such an effect in tissue culture then a stent placed in-vivo could alter or inhibit the restenotic activity in vessels subjected to angioplasty.
Vanderbilt University in conjunction with the Walter Reed Army Medical Center performed a series of experiments in porcine iliac and coronary models utilizing radioactive Strecker stents. First results in iliac model restenosis resulted in a 37% reduction in neointimal area in 32P 0.14 uCi stents vs controls one month post procedure. Further in-vivo testing performed with radioactive Palmaz-Schatz stents in porcine coronary models demonstrated as much as a 50% reduction in neointimal area and cross sectional area of stenosis one month post stent implantation.
Since these early reports, numerous other studies have been conducted which have demonstrated and substantiated these early findings.
Thus, there exists a need in the art for a suture having low level radioactive particle emissions for the reduction and possible elimination of smooth muscle cell proliferation and hence neointimal hyperplastic response in anastomotic vessel sites, thereby providing longevity to the life of the graft.